Late-life depression (LLD) is a prevalent mental disorder among older adults. Previous studies revealed that many pathologic factors are associated with the onset and development of LLD. However, the precise mechanisms that cause LLD remain elusive. Aging induces chronic inflammatory changes mediated by alterations of immune responses. The chronic systemic inflammation termed "inflammaging" is linked to the etiology of aging-related disorders. Aged microglia induce senescence-associated secretory phenotype (SASP) and transition to M1-phenotype, cause neuroinflammation, and diminish neuroprotective effects. In addition, there is an age-dependent loss of blood-brain barrier (BBB) integrity. As the BBB breakdown can lead to invasion of immune cells into brain parenchyma, peripheral immunosenescence may cause microglial activation and neuroinflammation. Therefore, it is suggested that these mechanisms related to brain inflammaging may be involved in the pathogenesis of LLD. In this review, we described the role of brain inflammaging in LLD. Pharmacologic approaches to prevent brain inflammaging appears to be a promising strategy for treating LLD.
Keywords: BBB breakdown; Inflammasome activation; Late-life depression; Metabolic reprogramming; Senescence-associated secretory phenotype (SASP).
© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.